Erythroblastosis fetalis is hemolytic anemia in the fetus or neonate

caused by transplacental transmission of maternal antibodies to fetal

RBCs. The disorder usually results from incompatibility between maternal
and fetal blood groups, often Rh0(D) antigens. Diagnosis begins with
prenatal maternal antigenic and antibody screening and may require
paternal screening, serial measurement of maternal antibody titers, and
fetal testing. Treatment may involve intrauterine fetal transfusion or
neonatal exchange transfusion. Prevention is Rh0(D) immune globulin
injection for women at risk.
Erythroblastosis fetalis classically results from Rh0(D) incompatibility, which
may develop when a woman with Rh-negative blood is impregnated by a
man with Rh-positive blood and conceives a fetus with Rh-positive blood
(see also Perinatal Hematologic Disorders: Hemolysis). Other fetomaternal
incompatibilities that can cause erythroblastosis fetalis involve the Kell,
Duffy, Kidd, MNSs, Lutheran, Diego, Xg, P, Ee, and Cc antigen systems,
as well as other antigens. Incompatibilities of ABO blood types do not
cause erythroblastosis fetalis.
Pathophysiology
Fetal RBCs normally move across the placenta to the maternal circulation
throughout pregnancy. Movement is greatest at delivery or termination of
pregnancy. Movement of large volumes (eg, 10 to 150 mL) is considered
significant fetomaternal hemorrhage; it can occur after trauma and
sometimes after delivery or termination of pregnancy. In women who have
Rh-negative blood and who are carrying a fetus with Rh-positive blood,
fetal RBCs stimulate maternal antibody production against the Rh antigens.
The larger the fetomaternal hemorrhage, the more antibodies produced.
The mechanism is the same when other antigen systems are involved;
however, Kell antibody incompatibility also directly suppresses RBC
production in bone marrow.
Other causes of maternal anti-Rh antibody production include injection with
needles contaminated with Rh-positive blood and inadvertent transfusion of
Rh-positive blood.
No complications develop during the initial sensitizing pregnancy; however,
in subsequent pregnancies, maternal antibodies cross the placenta and
lyse fetal RBCs, causing anemia, hypoalbuminemia, and possibly high-
output heart failure or fetal death. Anemia stimulates fetal bone marrow to
produce and release immature RBCs (erythroblasts) into fetal peripheral
circulation (erythroblastosis fetalis). Hemolysis results in elevated indirect
bilirubin levels in neonates, causing kernicterus (see Metabolic, Electrolyte,
and Toxic Disorders in Neonates: Kernicterus). Usually, isoimmunization
does not cause symptoms in pregnant women.
Diagnosis
• Maternal blood and Rh typing and reflex antibody screening
• Serial antibody level measurements and sometimes middle cerebral
artery blood flow measurements for pregnancies at risk
At the first prenatal visit, all women are screened for blood type, Rh type,
and anti-Rh0(D) and other antibodies that are formed in response to
antigens and can cause erythroblastosis fetalis (reflex antibody screening).
If women have Rh-negative blood and test positive for anti-Rh0(D) or they
test positive for another antibody that can cause erythroblastosis fetalis, the
father's blood type and zygosity (if paternity is certain) are determined. If he
has Rh-negative blood and is negative for the antigen corresponding to the
antibody identified in the mother, no further testing is necessary. If he has
Rh-positive blood or has the antigen, maternal anti-Rh antibody titers are
measured. If titers are positive but less than a laboratory-specific critical
value (usually 1:8 to 1:32), they are measured monthly until 24 wk, then
every 2 wk. If the critical value is exceeded, fetal middle cerebral artery
blood flow is measured at intervals of 1 to 2 wk depending on titers and
patient history; the purpose is to detect high-output heart failure, indicating
high risk of anemia. Elevated blood flow for gestational age should prompt
percutaneous umbilical blood sampling to obtain a sample of fetal blood. If
paternity is reasonably certain and the father is likely to be heterozygous
for Rh0(D), the fetus' Rh type is determined. If fetal blood is Rh positive or
status is unknown and if middle cerebral artery flow is elevated, fetal
anemia is likely.
Treatment
• Fetal blood transfusions
• Delivery at 32 to 34 wk
If fetal blood is Rh negative or if middle cerebral artery blood flow remains
normal, pregnancy can continue to term untreated. If fetal anemia is likely,
the fetus can be given intravascular intrauterine blood transfusions by a
specialist at an institution equipped to care for high-risk pregnancies.
Transfusions occur every 1 to 2 wk until fetal lung maturity is confirmed
(usually at 32 to 34 wk), when delivery should be done. Corticosteroids
should be given before the first transfusion if the pregnancy is > 24 wk,
possibly > 23 wk.
Neonates with erythroblastosis are immediately evaluated by a pediatrician
to determine need for exchange transfusion (see Perinatal Hematologic
Disorders: Perinatal Anemia).
Prevention
Prevention involves giving the mother
• Rh0(D) immune globulin at 28 wk gestation and within 72 h of
pregnancy termination
Delivery should be as atraumatic as possible. Manual removal of the
placenta should be avoided because it may force fetal cells into maternal
circulation.
Maternal sensitization and antibody production due to Rh incompatibility
can be prevented by giving the woman Rh0(D) immune globulin. This
preparation contains high titers of anti-Rh antibodies, which neutralize Rh-
positive fetal RBCs. Because fetomaternal transfer and likelihood of
sensitization is greatest at termination of pregnancy, the preparation is
given within 72 h after termination of each pregnancy, whether by delivery,
abortion, or treatment of ectopic pregnancy. The standard dose is 300 μg
IM. A rosette test can be used to rule out significant fetomaternal
hemorrhage, and if results are positive, a Kleihauer-Betke (acid elution) test
can measure the amount of fetal blood in the maternal circulation. If test
results indicate fetomaternal hemorrhage is massive (> 30 mL whole
blood), additional injections (300 μg for every 30 mL of fetal whole blood,
up to 5 doses within 24 h) are necessary.
Treatment at termination of pregnancy is occasionally ineffective because
sensitization occurred earlier during pregnancy. Therefore, at about 28 wk,
all pregnant women with Rh-negative blood and no known prior
sensitization are given a dose. Some experts recommend a 2nd dose if
delivery has not occurred by 40 wk. Rh0(D) immune globulin should also be
given after any episode of vaginal bleeding and after amniocentesis or
chorionic villus sampling. Anti-Rh antibodies persist for > 3 mo after one
dose.